Diagnosis and management of PMS
10 Oct 2006
An accurate diagnosis and treatment can relieve PMS and allow a return to normal life, writes Mr Nick Panay,Consultant in Obstetrics and Gynaecology at Queen Charlottte's and Westminster hospital.
PMS is defined as distressing physical, behavioural and psychological symptoms not due to organic disease which regularly recur during the same phase of each menstrual (ovarian) cycle and which disappear or significantly regress during the remainder of the cycle. Typical psychological symptoms include depression, anxiety, irritability and loss of confidence. Physical symptoms include bloating and mastalgia.
Many women will experience minor physical and emotional changes premenstrually.
However, in approximately 5 per cent of women, these symptoms are severe and can interfere with normal activities and lead to a breakdown in interpersonal relationships.
Diagnosis cannot be accurately established by retrospective recall. It needs to be made by the prospective logging of symptoms by the patient, ideally over two cycles.
A symptom questionnaire is the best way of documenting symptoms. The questionnaires should continue to be kept after treatment has been started to give an objective indication of response to therapy. It is important that lifestyle is optimised before any medical treatments are started. Reducing stress helps to ameliorate the symptoms. Dietary measures such as avoiding carbohydrate binges and limiting alcohol and caffeine intake are often of benefit. However, in moderate to severe PMS, medical therapy should be started sooner rather than later.
Alternative therapy
A recent meta-analysis showed no significant benefit in the treatment of severe PMS with progestogens and progesterone. Synthetic progestogens actually have PMS-like side-effects.
Natural progesterone could have benefits because it can have an anxiolytic effect and act as a mild diuretic. However, of the few underpowered studies conducted only one has shown benefit and better data are needed. One randomised placebo controlled study has shown that Vitex agnus castus is an effective treatment for women with PMS. The effects were confirmed by the women's self-assessment and by the investigators' evaluation. Tolerability of agnus castus was good; patient acceptance was high and side-effects were few and mild.
Data exist on the follicular phase of the ovarian cycle being lengthened by red clover isoflavones. This, coupled with benefits for menopausal symptoms has led to further research on the use of this product in the treatment of PMS in both pre- and perimenopausal women. My unit is expecting to publish data in the next year.
In a recent meta-analysis, insufficient data were available to give a recommendation for using vitamin B6 in the treatment of PMS. There is, therefore, no rationale for giving daily doses of vitamin B6 in excess of 100mg, especially following the recommendation from the DoH and Medicine Control Agency in 1999 to restrict the dose of vitamin B6 available generally to 10mg and to limit the dose sold by a pharmacist to less than 50mg.
One study showed significant improvements for women with severe PMS during treatment with bright white light from a face mask. The mechanism of action of light therapy in severe PMS is unknown and further data are required. Some investigations have linked severe PMS to disturbance in circadian rhythms and hence light therapy may act by correcting abnormal circadian rhythm.
Extensive trial data exist for St John's Wort as an anti-depressant. In a small pilot study in women with severe PMS, treatment resulted in a significant improvement of symptoms. Tolerance and compliance with the treatment was good. However, the absence of a placebo group in this trial limited the evaluation of the effectiveness of St John's Wort.
Medical treatment
The two main evidence-based medical treatments for moderate to severe PMS are ovulation suppression and SSRIs. Although it is able to suppress ovulation, and is used commonly to improve PMS symptoms, the combined oral contraceptive pill was not initially shown to be of benefit in randomised prospective trials. A new type of combined contraceptive pill contains an anti-mineralocorticoid and anti-androgenic progestogen, drospirenone. This is showing considerable promise in the treatment of severe PMS because it is devoid of progestogenic side-effects and has a mild diuretic and anti-androgenic effect.
There are now both observational and small randomised trial data supporting its efficacy. If the Pill is used to treat severe PMS, the packets should be used back-to-back (bicycling/tricycling or continuously) with a break only introduced if erratic bleeding occurs. An ovulation suppressant treatment of proven efficacy in a placebo-controlled trials which appears suitable for long-term usage is continuous 17 beta-oestradiol combined with cyclical progestogen. In one of the first studies, 200mu g oestradiol patches were tested against placebo in a cross-over trial and found to be highly effective. Both the physical and psychological symptoms of PMS were reduced by an average of 60 per cent. The standard dose is now 100mu g, which produces physiological mid-follicular oestradiol levels.
Progestogen intolerance
Oestradiol treatment for PMS requires the use of oral progestogens, such as norethisterone or dydrogesterone, to prevent endometrial hyperplasia. However, the side-effects from progestogens often lead to a reduction in efficacy and treatment discontinuation. The hormone released by the levonorgestrel intrauterine system acts locally to produce endometrial atrophy, with minimal systemic progestogenic side-effects.
GnRH analogues
Gonadotrophin releasing hormone (GnRH) analogue usage results in cycle suppression and elimination of pre-menstrual symptoms. However, because symptoms return with ovarian function, therapy would have to be continued indefinitely. This is precluded by significant trabecular bone loss which can occur with only six months of therapy.
The use of GnRH analogues with add-back HRT or tibolone is a useful option both to prevent vasomotor symptoms and bone loss; bone mineral density should be monitored in women using analogues for more than six months.
Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the ultimate form of ovulation suppression and the only true cure for PMS because this removes the ovarian cycle completely.
The procedure is only rarely performed for this indication, as a lesser alternative can usually be found. Preoperative GnRH analogues are a useful test of whether hysterectomy /oophorectomy will be successful in treating symptoms. It is essential that adequate hormone therapy is given (including consideration of testosterone replacement) to prevent simply replacing one set of symptoms with another.
SSRIs
There is now considerable evidence for the beneficial effects of SSRIs in treating PMS. Initial studies with fluoxetine showed it to be efficacious compared to placebo for treating pre-menstrual dysphoric disorder, or PMDD - the American Psychiatric Association's definition of severe PMS.
There now exists a wealth of data from other randomised controlled trials for the treatment of severe PMS with most types of SSRIs. Randomised studies have shown that half-cycle SSRI treatment is as effective as continuous administration.
The importance of this is that patients are less likely to develop dependence on this regime, benefit is immediate and patients are more likely to accept the treatment because it can be regarded as being different to the regimes used for psychiatric disorders.
One of the optimum regimes for treatment-resistant PMS is half-cycle citalopram, 20mg/day from day 15 to day 28 of the menstrual cycle. This appears to be effective even in women whose previous SSRI treatment has failed.
PMS continues to be poorly understood and in many cases inadequately managed. It is imperative that properly conducted research continues to be funded.
Mr Panay is chairman of National Association for Premenstrual Syndrome, director of West London Menopause and PMS Centre and consultant obstetrician and gynaecologist, Queen Charlotte's & Chelsea Hospital and Chelsea & Westminster Hospitals, London.
This article was published courtesy of GP Magazine. www.healthcarerepublic.com
MANAGEMENT OF PMS
First Line
· Combined continuous new generation pill Yasmin, Cilest
Second Line
· Oestradiol patches (100mu g) + oral progestogen duphaston 10mg D17-D28;
· or Mirena;
· or SSRIs such as half-cycle Citalopram 10-20mg D15 - D28
Third Line:
· GnRH analogues goserelin 3.6mg or leuprorelin 3.75mg and tibolone 2.5mg/day
· continuous combined low dose HRT
Fourth Line:
· TAH BSO + HRT (including testosterone)
RESOURCES
- Panay N. Management of premenstrual syndrome. Royal College of Obstetricians & Gynaecologists Green Top Guidelines. 2006 (In press) - National Association for Premenstrual Syndrome: advice for sufferers and health professionals.
- Visit website at: www.pms.org.uk.
